Article for diagnosis of achlorhydria

ABSTRACT

There is disclosed an article for diagnosis of achlorhydria which includes an agent which is readily detectable when released in the stomach, the agent being enclosed in a fluid-impervious entrapping medium which is degraded in acidic fluids to release the agent.

BACKGROUND OF THE INVENTION

Achlorhydria is a condition characterized by stomach fluids that are notacidic. Achlorhydria may be a disorder in itself whichcharacteristically produces symptoms of digestive problems. Frequentlyachlorhydria is a symptom of a different disorder such as cancer of thestomach or certain nervous disorders.

Achlorhydria is difficult to detect without an uncomfortable andprofessionally administered procedure. The procedure for detectingachlorhydria usually involves introduction of analysis or samplingdevices into the patient's stomach to provide either a direct reading ofstomach fluid pH or a sample for analysis. In either case, a tube mustbe inserted down the patient's throat which produces the usual problemsof patient resistance and gagging, and as a result tests forachlorhydria are adminstered far less frequently than they should be.

A simple, reliable, and comfortably administered test for achlorhydriais needed. If such a test were available, it could be given routinely aspart of regular medical checkups to provide an early warning for seriousstomach problems and a reliable indication of the acidity of a patient'sstomach fluid.

THE INVENTION

This invention is an inexpensive, reliable, easily administered articlethat is useful to detect the presence of stomach acid. The articleincludes a detection agent that is entrapped in a fluid-imperviousentrapping medium. The entrapping medium includes material that isdegradable at pH lower than 6 which, when degraded, permits the releaseof the entrapped detection agent from the entrapping medium.

A detection agent is normally a material which exerts little or nophysiological effect on the individual but its presence, when releasedfrom its entrapment, is easily determined. A typical detection agent ismethylene blue, which when released in the stomach, imparts acharacteristic color to the urine. Other substances which color theurine include phenol red and Pyridium (phenazopyridine HCl). Detectionagents which cause the patient's urine to fluoresce such as sodiumfluorescein, riboflavin, or quinine may be used. A detection agent maybe a substance not normally found in the urine or blood such as sodiumbromide, potassium iodide, or phenolphthalein. A detection agent such asmethyl mercaptan may cause the urine or stool to have an unusual odor. Adetection agent may color the stool. Examples of this type includeunabsorbable dyes, charcoal, bismuth subnitrate, manganese dioxide, orreduced iron. The drug Flagyl (metronidazole) may cause the patient toexperience an unusual taste. Potassium iodide, when released in thestomach, is detectable in the saliva. Sodium fluorescein will causediscoloration of the skin or sclera. The detection agent may be onewhose presence in the body in either compact (entrapped) or diffuse(released) form may be determined by mechanical means. Such detectionagents may be radioactive or radio-paque materials. Finally, thedetection agent may be a substance which produces an easily observablephysiological effect such as a flatulent, diuretic, myotic, ormidriatic.

The entrapping medium is one which is impervious to stomach fluids. Theentrapping medium includes a degradable element which is degradable whensubjected to stomach fluids at normal low pH. The entire entrappingmedium or only a portion of it may be degradable when that portion isadapted to release the entrapped agent when it is degraded.

The entrapping medium may be degraded by any degree of acidity, or itmay be degraded only in specific pH ranges. By suitable selection ofdegradable materials, a quantitative measure of a patient's stomachacidity may be obtained.

One suitable entrapping medium useful in this invention is based onmagnesium, either as the entrapping medium, per se, or as an integralpart of the entrapping medium which degrades in normal stomach acid torelease the detection agent entrapped in a fluid-impervious material. Asan example, an enclosure of rubber of suitable physiologically inertplastic may be sealed with a thin magnesium ribbon. At pH lower than2.3, the magnesium readily degrades to break the seal and release thedetection agent maintained within the rubber or plastic enclosure. Sincenormal stomach fluid is usually at a pH lower than 2.3, the magnesiumbased article of the present invention may readily detect normal stomachacidity for most patients simply by ingesting it and monitoring thepatient for the presence of the detection agent, for example, his urine,for a period of approximately twelve hours. If the patient has normalstomach acid, the ingested articles of this invention will degrade inthe patient's stomach releasing the detection agent, for example,methylene blue, which will color the patient's urine a characteristicgreen color within hours after ingestion.

If a patient suffering from achlorhydria ingests such an article of thisinvention, the high pH in the person's stomach -- normally above 6 --will not degrade the entrapping medium so that the detection agent, forexample, methylene blue, will pass through the patient's entiredigestion system within the entrapping medium, and the absence ofcolored urine will indicate that the patient is suffering fromachlorhydria. When stomach acid alone is the degrading medium, it isreferred to herein as an intrinsic degrading medium.

Another entrapping medium may include the combination of cellulose andthe enzyme cellulase which causes cellulose to degrade. Such anentrapping medium requires a pH between 3 and 6 to be degraded becausecellulase is not active to degrade cellulose at pH lower than 3 orhigher than 6. A cellulose-cellulase based entrapping medium could beingested with a quantity of antacid or buffering material so that anystomach acidity which would cause the patient's stomach fluids to be atpH lower than 6 would either be in the range at which cellulase woulddegrade cellulose at the time the article is ingested, or it would passthrough that range due to the action of the antacid in raising the pH ofthe stomach fluids. When a degrading medium is ingested with the articleof this invention rather than being already present in the stomach, sucha degrading medium is referred to herein as an extrinsic degradingmedium.

DETAILED DESCRIPTION OF THE INVENTION

The invention may be better explained with reference to the followingexamples which illustrate specific embodiments of the invention and areintended to be illustrative rather than limiting on its scope.

EXAMPLE 1

An article embodying this invention was prepared by filling a shortlength of rubber tubing with methylene blue crystals. The tubing wasselected to be one that is not permeable to the fluids found in a humandigestive tract. After being filled with methylene blue crystals, thetubing was rolled tightly and sealed by twisting a piece of thinmagnesium ribbon around the rolled tubing to prevent it from becomingunrolled. The magnesium ribbon was 0.006 inches thick, 0.0125 incheswide and long enough to perform its function of sealing the rolledrubber tubing.

A 100 ml quantity of 0.1 normal hydrochloric acid was placed in a beakeras a simulated stomach fluid. The rubber tubing sealed with magnesiumwas placed in the beaker. The methylene blue crystals were shielded fromthe hydrochloric acid solution as was evidenced by the fact that thehydrochloric acid remained a water white solution. In about 140 minutes,the magnesium tubing degraded, the rubber tube unrolled, and methyleneblue was released into the acid solution as could be observed by theappearance of a dark stain in the solution.

EXAMPLE 2

A number of detection devices embodying this invention were prepared inaccordance with Example 1. Several beakers were prepared to contain 100ml quantities of 0.1 normal hydrochloric aicd which had been titratedwith sodium hydroxide so that each beaker contained fluid at a differentpH. The pH in the respective beakers was 1, 2, 3, 4, 5, 6 and 7. Onedetection device was placed in each beaker. After a period of threehours, the detection devices in beakers containing fluid of pH 1 and pH2 had opened and the fluid was darkly stained by the methylene blue.After a period of 24 hours, the devices which were placed in beakershaving pH 3 and above had not opened.

EXAMPLE 3

The device embodying this invention was prepared in the form of athin-walled rubber tubing containing methylene blue crystals which wastightly rolled and bound with a strip of cellulose in the form of filterpaper. A 200 mg quantity of cellulase was maintained outside of theentrapping medium but as a portion of the device. The cellulase wasMeicelase-P enzyme, a trade name of Meiji Seika Kaisha Company of Tokyo,Japan, which is employed to identify a cellulase enzyme prepared fromtrichodermi viride fungi. A solution of 0.1 normal hydrochloric acid wastitrated to pH of 6.5 with sodium hydroxide. Into a 20 ml quantity ofthis solution, the device described hereinabove was placed, and thesolution was maintained at 37° C with slight agitation for a period ofeight hours. After the eight hour period, the device remained unopened,and the dye was not released from within the rubber tubing.

EXAMPLE 4

A device made in accordance with Example 3 was placed in 20 ml of asolution of 0.1 normal hydrochloric acid titrated to a pH of 2.5 withsodium hydroxide. The solution was maintained at a temperature of 37° C,and it was slightly agitated. After one-half hour in the solution, thedevice remained unopened, and the pH of the solution was adjusted withsodium hydroxide to 3.5. Agitation was continued for another half hour,and the packet still remained unopened. The pH was again adjusted withsodium hydroxide to 4.5. Each half hour the pH of the solution wasraised 1 pH increment. Before the pH of the solution reached 6, thepacket had opened, and the entrapped dye had been released.

It is evident from the foregoing description and examples that thepresent invention concerns any entrapping medium which includes adegradable element that is sensitive to acid and which contains adetection agent. Devices wherein the entrapping medium itself isdegradable in an acidic environment are within the scope of thisinvention. The invention also includes devices containing a number ofdifferent detection agents that are released at different pH levels sothat a diagnosis may be made not only of achlorhydria but also of adegree of hypochlorhydria, for example, for a patient suffering frominsufficient stomach acids rather than a complete absence of stomachacid.

This device may be used alone or in conjunction with drugs whichstimulate the secretion of hydrochloric acid such as histaminephosphate, caffeine, or betazole hydrochloride.

What is claimed is:
 1. An article useful to detect stomach acidcomprising a detection agent enclosed in a fluid-impervious entrappingmedium with said entrapping medium including a degradable element thatis degradable at pH lower than 6, with said degradable element sealingsaid entrapping medium whereby when said degradable element is degraded,said detection agent is released from said entrapping medium.
 2. Thearticle of claim 1 wherein said degradable element is degraded at pHlower than 2.3.
 3. The article of claim 2 wherein said degradableelement is magnesium.
 4. The article of claim 1 wherein said degradableelement is degraded between pH 3 and pH
 6. 5. The article of claim 4wherein said degradable element is a cellulase-degradable form ofcellulose and cellulase.
 6. The article of claim 1 wherein saiddetection agent is a dye that colors urine.
 7. The article of claim 6wherein said detection agent is methylene blue.
 8. The article of claim6 wherein said detection agent is phenol red.
 9. The article of claim 6wherein said detection agent is phenazopyridine hydrochloride.
 10. Thearticle of claim 1 wherein said detection agent causes urine tofluoresce.
 11. The article of claim 10 wherein said detection agent issodium fluorescein.
 12. The article of claim 10 wherein said detectionagent is riboflavin.
 13. The article of claim 10 wherein said detectionagent is quinine.
 14. The article of claim 1 wherein said detectionagent is chemically detectable in urine.
 15. The article of claim 14wherein said detection agent is phenolphthalein.
 16. The article ofclaim 1 wherein said detection agent is detectable in saliva.
 17. Thearticle of claim 16 wherein the detection agent is potassium iodide. 18.The article of claim 1 wherein the detection agent is a substance whichproduces a physiological effect.
 19. The article of claim 18 wherein thedetection agent is a myotic.
 20. The article of claim 18 wherein thedetection agent is a midriatic.
 21. The article of claim 1 wherein saiddetection agent is a radioactive material.
 22. The article of claim 1including a multiple of entrapping mediums, said entrapping mediumscontaining different detection agents and being sealed by degradableelements that are degraded at different pH levels.